The aims of this proposal are to complete a description of transcription unit design in eukaryotic cells by determining how and where RNA polymerase II (pol II) transcription ceases. The laboratory is in the process of shifting mainly to transcriptional control studies of pol II transcription units during differentiation. The material to be used is chiefly differentiating erythroblastic (erythroleukemia) cells in culture and normal fetal and adult liver cells. A program is described for the isolation and characterization of genes that are expressed primarily or exclusively in the liver followed by testing which of the sequences confer liver specificity when these genes are reintroduced into animals. Finally, various techniques for following liver specific characteristics will be applied to developing mice to track at a molecular level the earliest detectable markers for liver differentiation. The health relevance of basic studies of this type lies in the confidence that many diseases result from defects in gene regulation both in adult and developing tissues. (G)